Abstract:
AIMS:Ischaemic preconditioning (IPC) protects the heart against prolonged lethal ischaemia through a signalling cascade involving Akt, glycogen synthase kinase-3β (GSK-3β), and mitochondrial ATP-sensitive potassium channels (mitoK(ATP)). We previously demonstrated the involvement of the Wnt pathway in IPC in vivo via GSK-3β. A downstream target might be mammalian target of rapamycin (mTOR) since Wnt can impair tuberous sclerosis complex-2 (TSC2) phosphorylation by inhibiting GSK-3β. Here, we investigate whether the mTOR pathway is involved in cardioprotection. METHODS AND RESULTS:Isolated-perfused mouse hearts were subjected to IPC via four cycles of ischaemia/reperfusion or pharmacological preconditioning (PPC) by diazoxide, a selective mitoK(ATP) activator. IPC, like PPC, induced an inhibition/phosphorylation of GSK-3β through Akt activation. Preconditioning also induced phosphorylation of mTOR, p70S6K, and 4E-BP1 that correlated with a significant reduction in infarct size after 40-min ischaemia and 120-min reperfusion when compared with non-preconditioned controls. Preconditioning was impaired in GSK3 knock-in mice. In transgenic mice hearts overexpressing secreted frizzled protein 1 (sFRP1, a Wnt/Frz antagonist), GSK-3β phosphorylation, mTOR activation, and cardioprotection were impaired. Cardioprotection and its signalling were also inhibited by rapamycin (an mTOR inhibitor), 5-HD (a mitoK(ATP) blocker), and N-(2-mercaptopropionyl) glycine (MPG) as a reactive oxygen species (ROS) scavenger. CONCLUSIONS:We propose that the preconditioning signalling pathway involving an amplification loop results in a downregulation of GSK-3β and a constant opening of mitoK(ATP) with ROS generation to activate the mTOR pathway and induce cardioprotection. The disruption of the Wnt/Frz pathway by sFRP1 modulates this loop, inducing GSK-3β activation. This study provides evidence that cardioprotection involves both a pro-survival mTOR pathway and a developmental Wnt pathway targeting GSK-3β.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Vigneron F,Dos Santos P,Lemoine S,Bonnet M,Tariosse L,Couffinhal T,Duplaà C,Jaspard-Vinassa Bdoi
10.1093/cvr/cvr002subject
Has Abstractpub_date
2011-04-01 00:00:00pages
49-56issue
1eissn
0008-6363issn
1755-3245pii
cvr002journal_volume
90pub_type
杂志文章abstract:OBJECTIVE:The aim was to test for the presence of cAMPi activated and ATPo activated chloride conductances (ICl(cAMP) and ICl(ATP)) in mouse ventricular myocytes. METHODS:Membrane currents were measured in enzymatically dissociated ventricular myocytes using the whole cell configuration of the patch clamp technique. ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract:AIMS:Atrial fibrillation (AF) is a progressive cardiac arrhythmia that increases the risk of hospitalization and adverse cardiovascular events. There is a clear demand for more inclusive and large-scale approaches to understand the molecular drivers responsible for AF, as well as the fundamental mechanisms governing th...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa307
更新日期:2020-10-29 00:00:00
abstract:AIMS:Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp043
更新日期:2009-04-01 00:00:00
abstract:AIMS:Our previous studies demonstrated that inflammation contributes to atherosclerosis through disruption of the low density lipoprotein receptor (LDLr) pathway. However, this effect is overridden by rapamycin, which is an inhibitor of mammalian target of rapamycin (mTOR). This study investigated the role of the mTOR ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt203
更新日期:2013-12-01 00:00:00
abstract::The afterload dependency of relaxation rate was reappraised in isolated canine hearts both in isovolumic and isobaric contractions by using the reliable exponential method in which the asymptote LV pressure (P chi) is variable. This method provided a closer correlation (r = 0.999 +/- 0.001) between the measured LV pre...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.10.649
更新日期:1985-10-01 00:00:00
abstract:OBJECTIVE:Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), triadin, and calsequestrin. METHODS:To better understand the role of junctin in excitation-contraction coupling in the heart, we genera...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00432-2
更新日期:2003-08-01 00:00:00
abstract:AIMS:Exercise capacity is reduced in heart failure (HF) patients, due mostly to skeletal muscle abnormalities including impaired energy metabolism, mitochondrial dysfunction, fibre type transition, and atrophy. Glucagon-like peptide-1 (GLP-1) has been shown to improve exercise capacity in HF patients. We investigated t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw182
更新日期:2016-09-01 00:00:00
abstract:AIMS:Mobilization of stem cells/progenitors is regulated by the interaction between stromal cell-derived factor-1 (SDF-1) and its ligand, CXC chemokine receptor 4 (CXCR4). Statins have been suggested to ameliorate pulmonary arterial hypertension (PAH); however, the mechanisms involved, especially their effects on proge...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn244
更新日期:2009-01-01 00:00:00
abstract:OBJECTIVE:The function of angiotensin converting enzyme (ACE) at cell sites of high collagen turnover, such as heart valves, is uncertain. The aim of this study was to assess ACE and kininase-II-like activities and collagen turnover in cultured valvular interstitial cells of the adult rat heart. METHODS:The valvular i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::The distribution of neuropeptide Y (NPY) in the rat cardiovascular system has been examined by radioimmunoassay, chromatographic analysis of tissue extracts, and immunocytochemistry. High concentrations of NPY were identified throughout the heart and within the major blood vessels of the rat in particular in the renal...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.9.570
更新日期:1985-09-01 00:00:00
abstract:OBJECTIVE:Inhibitors of poly (ADP-ribose) synthetase (PARS) activity reduce the infarct size caused by regional myocardial ischaemia and reperfusion in the rabbit and rat in vivo. The mechanism of action of these inhibitors is unclear. Here we investigate the effects of the PARS inhibitor 3-aminobenzamide (3-AB) on inf...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00221-1
更新日期:1999-01-01 00:00:00
abstract:OBJECTIVES:Coronary artery often reoccludes after thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA). This reocclusion is thought to be due to in situ platelet activation mediated by thromboxane (Tx) A2 and thrombin; hence, aspirin and thrombin inhibitors are often used in patients with acute my...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::An investigation of changes in the Mg2+ -dependent, Na+ -K+ -stimulated sarcolemmal ATPase and of intracellular electrolytes in the left failing heart due to pressure overload (aortic banding) was carried out in dogs. There was no change in the sarcolemmal Mg2+ -ATPase of the left or right ventricle for the whole dura...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/13.2.95
更新日期:1979-02-01 00:00:00
abstract:AIMS:Antihypertensive drugs are included in the medical therapy of vascular Ehlers-Danlos syndrome (vEDS). The β-blocker celiprolol has been suggested to prevent arterial damage in vEDS, but the underlying mechanism remains unclear. It is also unknown whether the widely used angiotensin II receptor type 1 antagonist lo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz095
更新日期:2020-02-01 00:00:00
abstract:AIMS:It is well established that dysfunction of voltage-dependent ion channels results in arrhythmias and conduction disturbances in the foetal and adult heart. However, the involvement of voltage-insensitive cationic TRPC (transient receptor potential canonical) channels remains unclear. We assessed the hypothesis tha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr167
更新日期:2011-11-01 00:00:00
abstract:Aims:RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvx104
更新日期:2017-08-01 00:00:00
abstract:OBJECTIVE:Current guidelines are controversial regarding exercise intensity in cardiovascular prevention and rehabilitation. Although high-intensity training induces larger increases in fitness and maximal oxygen uptake (VO(2max)), moderate intensity is often recommended as equally effective. Controlled preclinical stu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.03.010
更新日期:2005-07-01 00:00:00
abstract:OBJECTIVE:Transiently altering the atrial activation sequence induces atrial memory, manifested as an altered atrial gradient as measured in electrocardiographic XYZ leads. We hypothesized that protracted periods of left atrial impulse initiation alter the atrial gradient in a manner predictive of arrhythmias. METHODS...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00536-4
更新日期:2003-11-01 00:00:00
abstract::Atrial fibrillation (AF) is the most common tachyarrhythmia in clinical practice. Over decades of research, a vast amount of knowledge has been gathered about the causes and consequences of AF related to cellular electrophysiology and features of the tissue structure that influence the propagation of fibrillation wave...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvw007
更新日期:2016-04-01 00:00:00
abstract::The voltage- and rate-dependence of the depression of the maximum rate of depolarisation (Vmax) by therapeutic concentrations of flecainide and lorcainide were studied in guinea-pig ventricle by standard microelectrode techniques. At normal resting potentials the drugs produced only minor depression of Vmax in the abs...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.5.251
更新日期:1983-05-01 00:00:00
abstract:UNLABELLED:This study hypothesized that female patients with chronic heart failure (CHF), similarly as previously reported for male patients, have a decreased proportion of type I (slow twitch) muscle fibers combined with fiber atrophy, and respond to exercise training with an increased muscular fiber area and performa...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00313-7
更新日期:1999-04-01 00:00:00
abstract::The therapeutic potential of Hedgehog (Hh) signalling agonists for vascular diseases is of growing interest. However, molecular and cellular mechanisms underlying the role of the Hh signalling in vascular biology remain poorly understood. AIMS:The purpose of the present paper is to clarify some conflicting literature...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa285
更新日期:2020-10-16 00:00:00
abstract:AIMS:Atherosclerotic vascular disease has an inflammatory pathogenesis. Heme from intraplaque hemorrhage may drive a protective and pro-resolving macrophage M2-like phenotype, Mhem, via AMPK and ATF1. The anti-diabetic drug metformin may also activate AMPK-dependent signalling. HYPOTHESIS:Metformin systematically indu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa171
更新日期:2020-07-15 00:00:00
abstract:OBJECTIVE:The aim was to further characterise an experimental model of preconditioning of isolated rabbit cardiomyocytes and to determine the role of adenosine receptor subtypes in initiation of the protective response. METHODS:Isolated myocytes were subjected to 5 min preincubation in the presence or absence of gluco...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.7.1049
更新日期:1994-07-01 00:00:00
abstract::Cardiomyocytes express a surprisingly large number of potassium channel types. The primary physiological functions of the currents conducted by these channels are to maintain the resting membrane potential and mediate action potential repolarization under basal conditions and in response to changes in the concentratio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa068
更新日期:2020-07-15 00:00:00
abstract::In the superior vena cava of anaesthetised open chest dogs the axial pressure gradient was measured simultaneously with the blood flow velocity under different preload conditions. Both pressure gradient and velocity curves showed distinct systolic and diastolic waves. Peak pressure gradient ranged between 26 and 93 Pa...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.12.935
更新日期:1986-12-01 00:00:00
abstract:OBJECTIVES:Cardiovascular disease is rare in premenopausal women, but increases after the menopause when hormone replacement therapy reduces coronary events. Vascular smooth muscle cell (SMC) proliferation and migration occur in atherosclerosis, restenosis and venous graft disease. We studied the effects of 17 beta-est...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00
abstract::Stroke, ischaemic stroke and subtypes of ischaemic stroke display substantial heritability. When compared with related vascular conditions, the number of established risk loci reaching genome-wide significance for association with stroke is still in the lower range, particularly for aetiological stroke subtypes such a...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvy068
更新日期:2018-07-15 00:00:00
abstract:OBJECTIVE:Cytokine induction of intercellular adhesion molecule-1 (ICAM-1) on cardiac myocytes may be a critical step in cardiac inflammation associated with acute myocardial infarction and myocarditis. The aim of this study was to investigate the involvement of monocyte chemoattractant protein-1 (MCP-1), a homologue o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.8.1258
更新日期:1994-08-01 00:00:00
abstract::The structural nature of fibrillar collagen involved in the replacement fibrosis which accompanies discrete areas of cell necrosis remains uncertain, as does its influence on the diastolic and systolic stiffness of the intact myocardium. This study, using 15 micron diameter microsphere embolisation of the rat myocardi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.8.655
更新日期:1989-08-01 00:00:00